Despite numerous randomized studies (DENALI, EVEREST, EVEREST II, MONT BLANC, PLANET) showing the benefit of photodynamic therapy alone and in combination with anti-VEGF agents for the treatment of neovascular age-related macular degeneration and in particular polypoidal choroidal vasculopathy (PCV), you will not hear your local pharmaceutical representative talking about it over a lunch, owing to FDA rules about only marketing what appears on a drug’s label.

The label for verteporfin (Visudyne; Bausch Health) states it is for the “treatment of predominantly classic, subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis.” Unfortunately, the best use of PDT is for PCV lesions, also known as a type 1 CNV, so almost always not predominantly classic. So, ironically, the best use of PDT in 2021 is off-label and is specifically addressed in the US label with the statement that “there is insufficient evidence to indicate verteporfin for the treatment of predominantly occult, subfoveal choroidal neovascularization.”

How did we get into this mess? The pivotal studies, called the Treatment of Age-related macular degeneration with Photodynamic Therapy (TAP) study and Verteporfin in Photodynamic Therapy (VIP) study, showed that the predominantly classic subgroup, based on fluorescein angiogram CNV criteria, had the greatest effect. Additional studies, including the Verteporfin in Minimally Classic Choroidal Neovascularization (VIM) study and the Verteporfin in Occult (VIO) study, which assessed verteporfin in patients who have occult with no classic subfoveal CNV, failed to change the label in the United States and removed occult lesions from the label in Europe, the Middle East, and Africa. With the advent of anti-VEGF agents, the use of PDT in predominantly classic lesions has waned.

Current retina teaching no longer uses these fluorescein angiography-based terms, instead classifying lesions into different subtypes depending on location above or below the RPE. Although some PCV lesions can certainly look predominantly classic, the absence of a label change from the numerous combination studies is based on the idea that the overall mean vision was the same with combination treatment compared to anti-VEGF monotherapy despite a dramatic reduction in the number of anti-VEGF injections. With no significant improvement in vision with combination therapy, no change in the label can occur.

Throughout Asia, where the prevalence of PCV is greatest, PDT is used routinely in clinical practice. The reduction in treatments and overall results in meta-analysis and numerous studies support the use of PDT in PCV. In Hawaii, PCV also predominates, and in this issue, Greg Kokame, MD, of Honolulu gives an amazing overview of PDT and PCV. Many residents and fellows have never performed or even seen PDT, and the lasers we use to activate the drug are falling into disrepair, so the use may continue to be reduced. This is unfortunate because the off-label therapy is amazing at reducing treatments in PCV. To get it on label would take a study that in today’s day and age would be almost impossible to recruit, leaving the situation as we have it unchangeable. RP